A genetics professor with a gene point mutation causing a peripheral myopathy who found the diagnosis via an internet search engine then sequenced her own exome to find and identify the cause at aged 45 As Director of the Institute for Cardiogenetics (ICG) at the University of Lübeck, Germany, Jeanette Erdmann is known for her investigative work into the underlying genetic factors of cardiovascular disease, published in Nature, Nature Genetics, and the New England Journal of Medicine. However, while Erdmann has spent much of her career successfully unravelling the genetics of the cardiovascular system, she has been living with a rare muscular condition that remained undiagnosed for over 40 years. As the second of three siblings, there was nothing in the Erdmann family background to indicate any health concerns. Although Erdmann’s parents were worried that their daughter was late in meeting childhood developmental milestones and wasn’t as robust or active as her peers, she could walk, run around, and ride a bike. Whenever the Erdmann’s consulted doctors or took their daughter to clinics their fears were dismissed, and physicians had little advice to offer other than to ‘wait and see’ or that ‘everything will turn out right in the end’. All this changed at the age of seven when her parents were told by one doctor that their daughter most probably had a kind of benign, as opposed to progressive, muscle disease and this became the default diagnosis for the next 40 years. Erdmann progressed through high school and on to university without having to make too many concessions to her condition. She elected to study biology with a focus on genetics, partly because of an interest and aptitude in this area but also because she wanted to understand more about human genetics in relation to her own situation. She wasn’t too hopeful of finding an answer because when she started out 25 years ago, exome sequencing had not been developed and prospects of finding answers were limited by knowledge and technology. When she embarked on a PhD at the Institute of Human Genetics in Bonn under the supervision of Professors Peter Propping and Markus M. Nöthen, her undiagnosed condition had little impact on her day-to-day activity or working life. Things began to change with the onset of fatigue, severe headaches, and fitful sleep. This time she went to a specialist, Professor Bernd Schönhofer, who recognized that her chest muscles had become weakened and deteriorated to such an extent that carbon dioxide was building up in her blood causing the headaches and fatigue. The physician recommended using non-invasive ventilation (NIV) at night, which came as a shock. She says: ‘This was a big change and it was initially very difficult for me to accept that I would need to use a ventilator at night for the rest of my life’. Despite her doubts, she adapted quickly, and the benefits of the ventilator soon became clear. The headaches and extreme fatigue stopped almost immediately after the first night on NIV, and she recovered her ability to function in the daytime. She finished her PhD thesis and worked as a postdoctoral Fellow in Berlin with Professor Vera Regitz-Zagrosek and in Regensburg with Professor Heribert Schunkert before moving with Schunkert to Lübeck where she started out as a group leader, assistant professor, became an associate, and finally a full Deutsche Zentrum für Herz-Kreislauf-Forschung (DZHK-German Centre for Cardiovascular Research)-Professor in Cardiovascular Genetics. In 2013, she became Director of the ICG founded by the University of Lübeck, with a staff of over 25. The Institute exists to bring together integrative and experimental approaches to further the understanding of the genetics of cardiovascular disease and is involved in large-scale consortia such as CARDIoGRAMplusC4D, which she currently co-chairs with Professor Sir Nilesh J. Samani from the University of Leicester, UK. The irony of her success in uncovering and elucidating the genetics behind cardiovascular diseases while her own condition remained undiagnosed was not lost on Erdmann. ‘Although there was some comfort in remaining undiagnosed, without a diagnosis there is no concrete future and by my mid-40s, I realized that it would be better to have a precise diagnosis as there might be a therapy available’. However, despite numerous tests and examinations none of the specialists she consulted could give her a definitive diagnosis. The answer, however, was very close to hand and arrived one sleepless night. ‘I woke up in the middle of the night feeling disappointed and frustrated and picked up my iPhone and started to search the Internet. I don’t know why I never did it before, but I entered a few search terms and the very first hits that came back were all concerned with Bethlem myopathy or Ullrich muscular dystrophy’. It was a Eureka moment Bethlem/Ullrich’s is characterized by weakened respiratory muscles, keloid scarring, and the use of a ventilator during sleep, all of which the search engine identified in seconds. To confirm the diagnosis, she decided to have her exome sequenced, which confirmed a most likely pathogenic mutation in the collagen 6A2 gene, one of the three genes that have been reported as disease genes for Bethlem myopathy/Ullrich muscular dystrophy or Collagen VI-related myopathy, by which the disease has become known. Further investigation of her parents confirmed that she was a spontaneous case. She became one of fewer than 300 people world-wide to have been identified with the condition. She is still not clear why standard medical practice failed to identify her condition for many years when the Internet was able to provide answers in seconds. While she remains cautious about using search engines for medical diagnosis, she acknowledges that for people with rare conditions, the breadth and depth of data on the Internet may offer an alternative way of researching rare disease. Having a diagnosis may be a long way from a cure but it means that the person affected can contact specialists and find out about potential therapies. She believes that living with a rare condition has helped her to focus on the patient as a person in her research work. She says: ‘Sometimes as scientists in the lab we are so fixated on looking for variations and mutations and getting to the next level scientifically that we can forget about the patient, but because I am also a patient, I try to avoid forgetting about the person behind the research’. After many years of investigating the genetics of complex cardiovascular disease, she has started to look into monogenic disorders such as Collagen VI-related myopathy with a view to muting the genes in question. She is also working on a new project with friend and former colleague from her time in Berlin, Johannes Holzmeister MD. She says: ‘It is early days, but we are planning something totally new and exciting which is working towards personalized therapies for orphan conditions such as mine. Our ongoing in vitro work suggests we can silence certain mutations and we hope soon to progress this to in vivo work. We will be forming a company and the first project is working on my own personalized therapy before moving on to other collagen VI mutations’ (for my fellow patients with Collagen VI-related myopathy). Erdman says she never envisaged the progress that she has seen in her work. ‘We are very close to therapies that we would never have thought possible in earlier decades, but I am quite sure that over the next 5 years there will be many examples of cures for monogenic diseases such as mine’. Orphan conditions are difficult to manage for those affected as information and support is scare, but this is an area where the Internet and social media have emerged in recent years to fill the void and offer positive advice and mutual support. Erdmann has herself benefitted from membership of such online support groups which attract a global community to share information and knowledge in the absence of anything else. These groups, she says, have helped her develop a sense of perspective about her condition. ‘There is a special group for people with Collagen VI-related myopathies where I have met some really inspiring people who all live fulfilling lives. Some have a hard time because collagen VI-related myopathy affects people across a broad spectrum, meaning that some can be so badly affected that they can never walk, while there are people in their 70s or even older living with the mutation who are relatively active and able to walk’. As someone who enjoys a highly productive and satisfying life, both personally and family-wise, she advises anyone with a rare condition, or children of parents who may be worried about their offspring to live for the moment and avoid focusing on the hope that things will change when a cure is discovered. ‘I would say try not to think about barriers, but really try to do whatever you want to do. Parents should encourage their children to have dreams and not to think about obstacles that might come up in the future. I never felt that that my condition made my career difficult, clearly it was not a benefit, but if I can do what I’ve done with this condition, then (almost) everything is possible’. Conflict of interest: none declared. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: firstname.lastname@example.org. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)
European Heart Journal – Oxford University Press
Published: Jun 7, 2018
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